The principal objective of this study is to determine the effect of ethanol on the metabolism of neurosteroids in the central nervous system. Neurosteroids such as 5a-pregnane-3a-ol-20-one (5a,3a-THP or Allopregnanolone) and 5a-pregnane-3a,21-diol-20-one(THDOC) have been shown to modulate the GABA/benzodiazepine binding sites and to exert anxiolytic and hypnotic effects. Modulation of these neurosteroids in the central nervous system by ethanol may be one of the underlying mechanisms for stress-related situations often observed in human alcoholics during withdrawal. The GC/MS-NCI technique that we have established for the measurements of trace levels of neurosteroids in human cerebro spinal fluids (CSF) has been extended to the analysis of human and rat plasma samples in this period. We were able to detect species differences from the levles of pregnenolone, 5a,3a-, 5b,3a-, 5a,3b-THP, androsterone and dihydrotestosterone in human and rat plasma samples. Among the four isoforms of THP, human plasma contains 5a,3a-, 5b,3a- and 5a,3b-THP at 70-150 picogram/ml concentrations while rat plasma contains only 5a,3a- and 5b,3b isomers at the similar concentration range. - mental health research, neurosciences, anxiety disorders, alcohol withdrawal, mass spectrometry, cerebrospinal fluid